Planta Med 2012; 78 - PD131
DOI: 10.1055/s-0032-1320489

Natural products as butyrylcholinesterase inhibitors – Screening of a small compound collection

D Karlsson 1, A Fallarero 1, I Busygin 2, 3, R Leino 2, P Vuorela 1
  • 1Pharmaceutical Sciences, Department of Biosciences, Abo Akademi University, Artillerigatan 6A, FI-20520 Turku, Finland
  • 2Laboratory of Organic Chemistry, Abo Akademi University, Biskopsgatan 8, FI-20500 Turku, Finland
  • 3Current location: BASF SE, Carl-Bosch-Strasse 38, 67056 Ludwigshafen, Germany

Investigation of the involvement of butyrylcholinesterase (BChE) in diseases such as Alzheimer's disease (AD), type 2 diabetes mellitus (T2DM) and multiple sclerosis (MS) makes it a valuable target for drug discovery. Cholinesterase inhibitors of natural origin have shown success in AD therapy and have encouraged further exploration of nature as a source of cholinesterase inhibitors. Using the Ellman's reaction a collection of 111 compounds containing commercially available compounds e.g. flavonoids and coumarins, as well as a subset of cinchona alkaloid derivatives synthesized by our group, were screened for anti-cholinesterase activity. Two cinchona alkaloids were found to inhibit the hydrolase activity of BChE in the micromolar range (IC50 ≤10µM) and were further characterized. Considering their wide medical use (mostly as antimalarials) the cinchona alkaloid scaffold may serve as an advantage in drug development for various diseases.